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Kunz, S.* ; Preuhsler, A.* ; Surianarayanan, S.* ; Dorn, B.* ; Bewersdorff, M. ; Alessandrini, F. ; Behrendt, R.* ; Karp, C.L.* ; Müller, W.* ; Martin, S.F.* ; Roers, A.* ; Jakob, T.*

T cell derived IL-10 is dispensable for tolerance induction in a murine model of allergic airway inflammation.

Eur. J. Immunol. 46, 2018-2027 (2016)

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Regulatory mechanisms initiated by allergen specific immunotherapy are mainly attributed to T cell-derived IL-10. However, it has not been shown that T cell-derived IL-10 is required for successful tolerance induction. Here, we analyze cellular sources and the functional relevance of cell type specific IL-10 during tolerance induction in a murine model of allergic airway inflammation. While tolerance induction was effective in IL-10 competent mice, neutralizing IL-10 prior to tolerogenic treatment completely abrogated the beneficial effects. Cellular sources of IL-10 during tolerance induction were identified by using transcriptional reporter mice as T cells, B cells and to a lesser extent DCs. Interestingly, tolerance induction was still effective in mice with T cell-, B cell-, B and T cell- or DC-specific IL-10 deficiency. In contrast, tolerance induction was not possible in mice lacking IL-10 in all hematopoetic cells, while it was effective in bone marrow chimera that lacked IL-10 only in non-hematopoetic cells. Taken together, allergen specific tolerance depends on IL-10 from hematopoetic sources. The beneficial effects of allergen specific immunotherapy cannot solely be attributed to IL-10 from T cells, B cells or even DCs, suggesting a high degree of cellular redundancy in IL-10 mediated tolerance.

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